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MDM2 as a Rational Target for Intervention in CDK4/6 Inhibitor Resistant, Hormone Receptor Positive Breast Cancer

Abstract

With the adoption of inhibitors of cyclin dependent kinases 4 and 6 (CDK4/6i) in combination with endocrine therapy as standard of care for the treatment of advanced and metastatic estrogen receptor positive (ER+) breast cancer, the search is now on for novel therapeutic options to manage the disease after the inevitable development of resistance to CDK4/6i. In this review we will consider the integral role that the p53/MDM2 axis plays in the interactions between CDK4/6, ERalpha, and inhibitors of these molecules, the current preclinical evidence for the efficacy of MDM2 inhibitors in ER+ breast cancer, and discuss the possibility of targeting the p53/MDM2 via inhibition of MDM2 in the CDK4/6i resistance setting.

Type Journal
ISBN 2234-943X (Print) 2234-943X (Linking)
Authors Portman, N.; Chen, J.; Lim, E.
Responsible Garvan Author Prof Elgene Lim
Publisher Name Frontiers in Oncology
Published Date 2021-11-30
Published Volume 11
Published Pages 777867
Status Published in-print
DOI 10.3389/fonc.2021.777867
URL link to publisher's version https://www.ncbi.nlm.nih.gov/pubmed/34804982